Compositions for Regenerating Defective or Absent Myocardium

Abstract

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation-In-Part application of U.S. application Ser. No. 11 / 448,351, filed on Jun. 6, 2006, which is a Divisional application of U.S. application Ser. No. 11 / 182,551, filed on Jul. 15, 2005.FIELD OF THE INVENTION[0002]The invention relates to tissue engineering generally, and more specifically to compositions and methods for regenerating defective or absent myocardium.BACKGROUND OF THE INVENTION[0003]Heart failure occurs in nearly 5 million people a year in the U.S. alone at a combined cost of about $40 billion annually for hospitalization and treatment of these patients. The results of all the effort and cost are disappointing with a 75% five year mortality rate for the heart failure victims. Treatments for chronic heart failure include medical management with pharmaceutical drugs, diet and exercise, transplantation for a few lucky recipients, and mechanical assist devices, which are costly and risk failure and...

AI Technical Summary

Benefits of technology

The invention provides a composition for regenerating defective or absent myocardium and restoring cardiac function. The composition includes an extracellular matrix (ECM) scaffold derived from a mammalian source, a protoeglycan, and a drug. The drug can be an antiarrhythmic agent, an antiinflammatory, a narcotic analgesic, or an antiinflammatory. The composition can be used to treat cardiac conditions caused by damage or absence of myocardium.

Problems solved by technology

The results of all the effort and cost are disappointing with a 75% five year mortality rate for the heart failure victims.

Treatments for chronic heart failure include medical management with pharmaceutical drugs, diet and exercise, transplantation for a few lucky recipients, and mechanical assist devices, which are costly and risk failure and infection.

Medical researchers have transplanted human hematopoetic stem cells, mesenchymal stem cells, endothelial precursor cells, cardiac stem cells, and skeletal myoblasts or bone marrow cells to the myocardium, with however little or mixed success in satisfactory regeneration of the myocardium.

As yet, the experiments to prove these theories have not worked sufficiently to be attempted in humans.

Meanwhile, typical structural abnormalities or damage to the heart that would lend itself to tissue regenerative therapies, were they available, include atrial septal defects, ventricular septal defects, right ventricular out flow stenosis, ventricular aneurysms, ventricular infarcts, ischemia in the myocardium, infarcted myocardium, conduction defects, conditions of aneurysmic myocardium, ruptured myocardium, and congenitally defective myocardium, and these defective conditions remain untreated in humans by any current tissue regenerative techniques.

Although tissue regeneration has been accomplished by transplantation in mammalian tissues such as the endocranium, the esophagus, blood vessels, lower urinary tract structures, and musculotendinous tissues, heart tissue regeneration by foreign tissue explant has remained a challenge.

One problem exists in the preparation of extracellular scaffolds in that they must be non-immunogenic and thus acellular before implantation.

Getting rid of the cells in the matrix may also inadvertently strip the scaffold of key bioactive proteins.

No experimentation has been conducted to date on regenerating mammalian myocardium using an emulsified or injectable extracellular matrix formulation.

The disadvantage of using intact, non-emulsified extracellular matrix compositions such as patches or strips is that placement of the material requires open surgery, with its coordinate risk of infection, challenge of access to the site, and longer recovery for the patient post-procedure.

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